2023 Fiscal Year Annual Research Report
Directing Human Induced Pluripotent Stem Cell-Derived Embryonic-like Organoid with 3D Biomimetic Cryogel Mechanical Microenvironment for Neural Induction.
| Project/Area Number |
22K20642
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Vadivelu RajaKumar 国立研究開発法人理化学研究所, 開拓研究本部, 基礎科学特別研究員 (60963543)
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Keywords | hIPSCs / Cryogel / Mechanobiology / Gastruloid / Axial patterning / Neuromesodermal |
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| Outline of Annual Research Achievements |
The use of Human-induced pluripotent stem cells (hiPSCs) to generate a synthetic embryonic model deemed “gastruloids” is new. Promising to recapitulate embryogenesis in vitro that overcomes ethical boundaries and the inaccessibility of studying implanted embryos in utero. The three dimensional (3D) gastruloids mimic some essential aspects of gastrula-stage embryos including post-gastrulation and the body plan of the developing embryo known as axial patterning. However, gastruloid model lacks the mechanical constrain of extraembryonic tissue (EXT). Hence, imperfect to capture early organogenesis. This study presents a simple agarose cryogel-based in vitro model that provides a mechanical microenvironment (stiffness and roughness) to direct the differentiation hiPSCs. Mechanistically, the softer and rougher topology cryogel gives rise to assemblies of the embryonic domain featuring co-development of neuroectoderm (OTX2) and mesoderm (T-Bra) lineages extending along the entire anterior-posterior axis. We found that N-cadherin is involved in generating the Otx2/t-Bra+ region which contributes to neuromesodermal progenitor identity. To further evaluate the co-development of mesodermal and neuroectoderm, we assessed the expression of Epha-1, which is shown to be a marker for neuromesodermal progenitors (NMPs) and associated with axial progenitors. We thus postulate that this gastruloids model may serve as a potential source to achieve neuromesodermal morphogenesis.
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